Pyrrole-2-carbonitriles are useful as intermediates in the production of chemical compounds, including pharmaceutical and insecticide compositions. See, for example, U.S. Pat. No. 6,492,402 (directed to thrombin inhibitors) and U.S. Pat. No. 5,204,332 (directed to pyrrole carbonitrile insecticidal, acaricidal and molluscicidal agents).
Barnett, et al., J. Can. Chem. 1980, 58, 409, teaches a synthetic process for 1-methylpyrrole-2-carbonitrile involving the reaction of 1-methylpyrrole with chlorosulfonyl isocyanate in dichloromethane in a first step. In Barnett's process, the product of the first step was reacted with DMF, and the reaction mixture was then poured into ice-cold 4M HCl. Following product workup and vacuum distillation, 1-methylpyrrole-2-carbonitile was said to be obtained in 58% yield.
Other synthetic methods for 1-methylpyrrole-2-carbonitrile from 1-methylpyrrole are said to include reaction with methanolic cyanide solution under anoidic oxidation conditions (J. Am. Chem. Soc. 1977, 99, 6111), reaction with excess 1,4-dicyanobenzene as a photosensitizer in the presence of methanolic cyanide solution (J. Chem. Soc., Chem. Commun. 1978, 1108), reaction of trimethylsilyl cyanide in a tetraphenylphorphine-sensitized photooxidation at −70° C. (J. Am. Chem. Soc. 1985, 107, 5279), and reaction with freshly prepared Ph3P(SCN)2 at −40° C. (J. Chem. Soc., Perkin Trans. I 1980, 1132). Another synthetic process starts with 2-pyrrolecarboxaldehyde (Can. J. Chem. 1959, 37, 2053 and J. Chem. Soc., Chem. Commun. 1972, 1226). Yet another process uses 2-pyrrolecarboxaldehyde as the starting material (J. Prakt. Chem. 1994, 336, 467 and Tetrahedron Lett. 1993, 34, 141). Such processes require tedious aqueous workup and repetitive extractions with ether, methylene chloride, or some other suitable solvent. Some procedures require the use of chromatography in the isolation/purification step.